The molecular signature of BCR-ABL fusion in chronic myeloid leukemia (CML) provides a unique tool for diagnosis and monitoring of tumor burden during therapy. The gold standard in this regard is conventional bone marrow cytogenetics. Peripheral blood fluorescent in situ hybridization (FISH) offers the possibility of a less invasive, more practical alternative method in terms of both cost and turnaround time. In the present study, we examined 296 paired samples from 65 patients with CML and demonstrate a tight correlation, in quantifying BCR-ABL burden between bone marrow cytogenetics, bone marrow dual color, double fusion (D-FISH), and peripheral blood D-FISH (P < 0.0001 for each). Furthermore, we demonstrate that peripheral blood D-FISH can be used as a surrogate for cytogenetic studies in monitoring cytogenetic remission status.