diff --git a/mypy/expandtype.py b/mypy/expandtype.py
index fd507216a6be..af436c3b465f 100644
--- a/mypy/expandtype.py
+++ b/mypy/expandtype.py
@@ -392,9 +392,11 @@ def expand_unpack(self, t: UnpackType) -> list[Type]:
             or isinstance(repl, TypeVarTupleType)
         ):
             return [UnpackType(typ=repl)]
-        elif isinstance(repl, (AnyType, UninhabitedType)):
+        elif isinstance(repl, (AnyType, UninhabitedType, UnionType)):
             # Replace *Ts = Any with *Ts = *tuple[Any, ...] and same for Never.
             # These types may appear here as a result of user error or failed inference.
+            # Unions may be inferred from e.g. conditional expressions used as type
+            # arguments (GH#22108) — carry them over instead of crashing.
             return [UnpackType(t.type.tuple_fallback.copy_modified(args=[repl]))]
         else:
             raise RuntimeError(f"Invalid type replacement to expand: {repl}")
diff --git a/mypy/test/testtypes.py b/mypy/test/testtypes.py
index b287e82b3d4a..dc667787c583 100644
--- a/mypy/test/testtypes.py
+++ b/mypy/test/testtypes.py
@@ -297,6 +297,15 @@ def test_expand_naked_type_var(self) -> None:
         self.assert_expand(self.fx.t, [(self.fx.t.id, self.fx.a)], self.fx.a)
         self.assert_expand(self.fx.t, [(self.fx.s.id, self.fx.a)], self.fx.t)
 
+    def test_expand_unpack_union_replacement(self) -> None:
+        # GH#22108: expanding *Ts with a union replacement (e.g. inferred from a
+        # conditional expression) must not crash expand_unpack — the union is
+        # carried over into the expansion, same as the Any/Never replacements.
+        union_repl = UnionType([self.tuple(UnpackType(self.tuple(self.fx.anyt))), self.fx.anyt])
+        orig = self.tuple(UnpackType(self.fx.ts))
+        exp = mypy.expandtype.expand_type(orig, {self.fx.ts.id: union_repl})
+        self.assertIn("Any", str(exp))
+
     def test_expand_basic_generic_types(self) -> None:
         self.assert_expand(self.fx.gt, [(self.fx.t.id, self.fx.a)], self.fx.ga)