A hospital-based case-control study was done to examine the hypothesis that persons with a family history of multiple myeloma (MM) or other cancers are at increased risk of multiple myeloma. Study members were 439 cases of multiple myeloma and 1317 matched controls seen at the Duke University Medical Center. Only 3 cases and 4 controls reported multiple myeloma in their families. The relative risk (RR) was 2.3, but the 95% confidence interval (CI) was 0.5-10.1, allowing no firm conclusion about the risk associated with familial MM. A family history of cancer of any type resulted in a relative risk of MM of 1.4 (CI: 1.1-1.8). This association was strongest (RR = 2.5, CI: 1.1-5.3) among young study members (age less than or equal to 49). A family history of hematologic malignancy (ICD 200-208) resulted in a RR of 2.4 (95% CI: 1.4-4.0). The data also suggested that a family history of lung cancer, breast cancer, and genitourinary cancer may be associated with increased risk of myeloma in older persons.