Prior studies have suggested that loss of plasma cell CD56 expression in multiple myeloma defines a unique patient subset and that CD56 expression reliably discriminates between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). We conducted a study of 68 untreated patients with MM from a single institution to define the clinicopathological correlates of CD56 expression. We find CD56 expression in 55 percent of MM. Lack of CD56 expression does not define a unique clinicopathological or prognostic entity in MM. Strong CD56 expression can also be found in MGUS and does not help to distinguish from MM.