The frequency of solid tumors was evaluated in 628 consecutive patients with multiple myeloma who had been treated with various melphalan-prednisone combinations. Among those patients who lived at least 2 months, the incidence and diversity of second tumors were similar to those in normal persons of the same age and duration at risk. The diagnosis was usually made within 2 years after the start of chemotherapy for the myeloma. Long-term melphalan therapy did not seem to contribute to the pathogenesis of second solid tumors in patients with multiple myeloma.