In order to identify myeloma cells and their precursor cells, we studied bone marrow samples from 39 patients with multiple myeloma, including 2 with plasma cell leukemia, using dual parameter cytometry of both DNA and cytoplasmic immunoglobulin (Cyt-Ig). Myeloma cells from 25 patients (64.1%) were aneuploid and those from the remaining 14 patients were diploid. In 25 patients with aneuploid myeloma, we found a small component of cells which had aneuploid DNA content without Cyt-Ig in addition to myeloma cells showing aneuploidy with Cyt-Ig. These aneuploid Cyt-Ig-negative cells were considered to be clonally involved because they were aneuploid, and detected predominantly in patients with stage III myeloma. This suggests that these cells may contribute to disease progression. The characteristics of these cells are described and the relationship between these cells and myeloma precursor cells is discussed.