diff --git a/compiler/src/dotty/tools/dotc/core/Types.scala b/compiler/src/dotty/tools/dotc/core/Types.scala
index 7e0867f087eb..73a26d6c7c85 100644
--- a/compiler/src/dotty/tools/dotc/core/Types.scala
+++ b/compiler/src/dotty/tools/dotc/core/Types.scala
@@ -2572,7 +2572,20 @@ object Types extends TypeUtils {
     }
 
     private def memberDenot(prefix: Type, name: Name, allowPrivate: Boolean)(using Context): Denotation =
-      if (allowPrivate) prefix.member(name) else prefix.nonPrivateMember(name)
+      // We need a valid prefix for `asSeenFrom`, as in `memberBasedOnFlags`.
+      val pre0 = prefix match
+        case prefix: ClassInfo => prefix.appliedRef
+        case prefix => prefix.widenIfUnstable
+      // When the prefix of a term selection is not a legal prefix, the typer computes the
+      // member as seen from a skolem of the prefix, so that a member type that mentions the
+      // prefix stays precise (see `TypeAssigner.maybeSkolemizePrefix`). Recomputing the
+      // denotation here -- after unpickling, most importantly -- has to skolemize the same
+      // way, or the reference silently acquires a more approximate info than the one it was
+      // pickled with, and the tree no longer survives a pickling round-trip.
+      val pre =
+        if name.isTermName && !TypeOps.isLegalPrefix(pre0) then QualSkolemType(pre0)
+        else pre0
+      prefix.findMember(name, pre, excluded = if allowPrivate then EmptyFlags else Private)
 
     private def argDenot(param: TypeSymbol)(using Context): Denotation = {
       val cls = param.owner
diff --git a/compiler/src/dotty/tools/dotc/inlines/Inliner.scala b/compiler/src/dotty/tools/dotc/inlines/Inliner.scala
index 998cb0b945e4..8b8132e24923 100644
--- a/compiler/src/dotty/tools/dotc/inlines/Inliner.scala
+++ b/compiler/src/dotty/tools/dotc/inlines/Inliner.scala
@@ -963,7 +963,18 @@ class Inliner(val call: tpd.Tree)(using Context):
       // For instance in tests/pos/i22070 when we type `Featureful[?]#toFeatures`,
       // `selectionType` will skolemize the prefix, find the denotation,
       // and then set that denotation for the `TermRef(Featureful[?], symbol toFeatures)`.
-      val reselectedType = selectionType(tree, qual1)
+      // But skip it when it cannot select anything else than what we already have: for an
+      // unstable prefix `selectionType` creates a *fresh* skolem on every call (see
+      // `maybeSkolemizePrefix`), and since the `NamedType` it returns is shared, computing
+      // it again silently changes the meaning of the types that were derived from the
+      // previous denotation. That is how the same selection ended up carrying two different
+      // skolems in i26681.
+      val reselectedType = tree.typeOpt match
+        case tpe: NamedType
+        if tpe.denotationIsCurrent
+           && skolemizesPrefix(tpe.prefix, tree.name)
+           && tpe.prefix == qual1.tpe.widenIfUnstable => tpe
+        case _ => selectionType(tree, qual1)
 
       def isConcreteImplementationOf(reselected: Symbol, overridden: Symbol)(using Context): Boolean =
         reselected.isTerm
diff --git a/compiler/src/dotty/tools/dotc/typer/TypeAssigner.scala b/compiler/src/dotty/tools/dotc/typer/TypeAssigner.scala
index d8f7dd32c9bd..1fe8ae1a0a77 100644
--- a/compiler/src/dotty/tools/dotc/typer/TypeAssigner.scala
+++ b/compiler/src/dotty/tools/dotc/typer/TypeAssigner.scala
@@ -120,11 +120,20 @@ trait TypeAssigner {
    *  @see QualSkolemType, TypeOps#asSeenFrom
    */
   def maybeSkolemizePrefix(qualType: Type, name: Name)(using Context): Type =
-    if (name.isTermName && !TypeOps.isLegalPrefix(qualType))
+    if skolemizesPrefix(qualType, name) then
       QualSkolemType(qualType)
     else
       qualType
 
+  /** Does selecting `name` on `qualType` skolemize the prefix?
+   *
+   *  Callers that may compute a selection type more than once need this: each call to
+   *  `maybeSkolemizePrefix` makes a *fresh* skolem, so for such a selection recomputing
+   *  the type is not a no-op even when it finds the very same member.
+   */
+  def skolemizesPrefix(qualType: Type, name: Name)(using Context): Boolean =
+    name.isTermName && !TypeOps.isLegalPrefix(qualType)
+
   /** The type of the selection `tree`, where `qual1` is the typed qualifier part. */
   def selectionType(tree: untpd.RefTree, qual1: Tree)(using Context): Type =
     val qualType =
diff --git a/tests/neg/i26681b.scala b/tests/neg/i26681b.scala
new file mode 100644
index 000000000000..845cb82410e2
--- /dev/null
+++ b/tests/neg/i26681b.scala
@@ -0,0 +1,25 @@
+// https://github.com/scala/scala3/issues/26681
+//
+// Selecting on an unstable prefix skolemizes that prefix, and each selection must
+// get its *own* skolem: two evaluations of `unstable` return two different `Owner`s,
+// so their `w` are unrelated and `Box[w.type]` must not unify across occurrences.
+//
+// Memoizing the `QualSkolemType` per prefix type would make `maybeSkolemizePrefix`
+// idempotent -- which is tempting, since a fresh skolem per call is what made the
+// same selection carry two different skolems in i26681 -- but it also makes every
+// case below compile. This test pins the property so that stays visible.
+class Box[T](val x: T)
+
+class Owner:
+  val w: Int = 8
+  val b: Box[w.type] = new Box(w)
+  def get: Box[w.type] = new Box(w)
+  def set(bb: Box[w.type]): Unit = ()
+
+def unstable: Owner = new Owner
+
+def same[T](a: Box[T], b: Box[T]): Unit = ()
+
+def t1 = same(unstable.b, unstable.b) // error
+def t2 = same(unstable.get, unstable.get) // error
+def t3 = unstable.set(unstable.get) // error
diff --git a/tests/run/i26681.check b/tests/run/i26681.check
new file mode 100644
index 000000000000..79ebd0860f49
--- /dev/null
+++ b/tests/run/i26681.check
@@ -0,0 +1,2 @@
+ok
+ok
diff --git a/tests/run/i26681.scala b/tests/run/i26681.scala
new file mode 100644
index 000000000000..f409aef89978
--- /dev/null
+++ b/tests/run/i26681.scala
@@ -0,0 +1,23 @@
+// https://github.com/scala/scala3/issues/26681
+class Box[T]
+
+class Owner:
+  val w: Int = 8
+  val b: Box[w.type] = new Box[w.type]
+
+def use[T](b: Box[T]): String = "ok"
+
+def unstable: Owner = new Owner
+
+transparent inline def f(inline rhs: Any): Any =
+  inline rhs match
+    case r: Box[t] => use[t](r)
+
+@main def Test =
+  // `unstable.b` has an unstable prefix, so its type is `Owner#b`, whose info is
+  // computed by skolemizing the prefix. Retyping the selection while inlining used
+  // to create a second skolem and overwrite the denotation of `Owner#b`, so the type
+  // `t` inferred when reducing the inline match no longer matched the scrutinee.
+  println(f(unstable.b))
+  val o = unstable
+  println(f(o.b))