We investigated the molecular cytogenetic features in myofibroblastic sarcoma (MS) to gain insight into the nature of the controversial entity. DNA copy number changes were analyzed by comparative genomic hybridization in 29 cases of MS and 5 cases of nodular fasciitis. The characteristic chromosomal imbalances in MS were gains at 1p11 --> p36.3 (19/29 [66%]), 12p12.2 --> p13.2 (13/29 [45%]), 5p13.2 --> p15.3 (9/29 [31%]), and chromosome 22 (8/29 [28%]) and loss at 15q25 --> q26.2 (7/29 [24%]). In contrast, only 1 of 5 cases of nodular fasciitis showed genetic aberrations. The average number of aberrations in nodular fasciitis (0.4) was significantly lower than that in MS (5.4). Thus, MS displayed complex DNA copy number changes and shared no range of common chromosomal abnormality with nodular fasciitis, indicating that distinct genetic pathways may be involved in the development of these entities.