Hairy cell leukemia (HCL) and multiple myeloma (MM) are well-described disease entities with characteristic clinical and pathologic features. We describe two patients initially treated for MM in whom atypical clinical and morphologic features subsequently developed that raised the possibility of HCL. Although the cytologic appearance and immunophenotype were not diagnostic of HCL, these cases challenge the criteria used to diagnose MM, HCL, and other recently described villous neoplasms.