diff --git a/spec/compiler/semantic/tuple_spec.cr b/spec/compiler/semantic/tuple_spec.cr
index 56afb4a0dd36..03444c8acd89 100644
--- a/spec/compiler/semantic/tuple_spec.cr
+++ b/spec/compiler/semantic/tuple_spec.cr
@@ -289,4 +289,15 @@ describe "Semantic: tuples" do
       ),
       "tuple too big"
   end
+
+  it "doesn't unify tuple metaclasses (#5384)" do
+    assert_type(%(
+      Tuple(Int32) || Tuple(String)
+      )) {
+      union_of(
+        tuple_of([int32] of Type).metaclass,
+        tuple_of([string] of Type).metaclass,
+      )
+    }
+  end
 end
diff --git a/src/compiler/crystal/semantic/type_merge.cr b/src/compiler/crystal/semantic/type_merge.cr
index 2ec8d3a9be07..dfc931da14ce 100644
--- a/src/compiler/crystal/semantic/type_merge.cr
+++ b/src/compiler/crystal/semantic/type_merge.cr
@@ -252,12 +252,14 @@ module Crystal
 
   class GenericClassInstanceMetaclassType
     def common_ancestor(other : MetaclassType | VirtualMetaclassType | GenericClassInstanceMetaclassType)
-      if instance_type.module? || other.instance_type.module?
-        nil
-      else
-        common = instance_type.common_ancestor(other.instance_type)
-        common.try &.metaclass
-      end
+      # Modules are never unified
+      return nil if instance_type.module? || other.instance_type.module?
+
+      # Tuple instances might be unified, but never tuple metaclasses
+      return nil if instance_type.is_a?(TupleInstanceType) || other.instance_type.is_a?(TupleInstanceType)
+
+      common = instance_type.common_ancestor(other.instance_type)
+      common.try &.metaclass
     end
   end