The gene encoding MUM1 was characterized as a possible translocation partner in chromosomal abnormalities involving a significant number of multiple myelomas. The overexpression of the MUM1 protein as a result of translocation t(6;14) (p25;q32) identified MUM1 as a putative regulatory molecule involved in B-cell differentiation and tumorigenesis. The expression of MUM1 protein in multiple myelomas supports this hypothesis. In the current study, using tissue microarray technology, we have tested the expression of the MUM1 protein in 1335 human malignancies and normal tissues. Our data show that the MUM1 protein is expressed in a wide spectrum of hematolymphoid neoplasms and in malignant melanomas but is absent in other human tumors. In addition, in tissue microarrays as well as in conventional paraffin sections, MUM1 staining was found to lack specificity in detecting plasmacytic differentiation as compared with two markers, CD138/Syndecan and VS38, commonly used in paraffin immunohistochemistry for detection of plasma cells.