Conventional cytogenetic analysis is limited in the evaluation of plasma cell disorders because, relative to normal hematopoietic elements, plasma cells divide slowly. Moreover, it is difficult to know whether abnormal metaphases originate from malignant plasma cells or myeloid cells harboring other abnormalities. We studied a patient with primary systemic amyloidosis who had previously been treated with an alkylating agent. Bone marrow cells were analyzed by cytoplasmic-immunoglobulin fluorescent staining combined with fluorescent in situ hybridization (cIg-FISH). Both chromosome enumeration probes for chromosome 1 and 7 and loci-specific probes for the short and long arm of chromosome 7 were used. Cytogenetic analysis disclosed the following abnormality: +der(1;7)(q10;p10). On cIg-FISH, the myeloid cells had fusion signals between chromosome enumeration probes for chromosomes 1 and 7, whereas plasma cells had the normal appearance of two pairs of signals. There was a second clone of abnormal myeloid cells with monosomy of chromosome 7. The bone marrow did not show any evidence of myelodysplasia. Interphase cIg-FISH is a useful technique for assigning the lineage of chromosomal abnormalities in plasma cell disorders.