Ossifying fibromyxoid tumor of soft parts (OFMT) is a rare soft tissue neoplasm of uncertain differentiation. Very recently recurrent rearrangements of the PHF1 gene have been reported in OFMT, including typical, atypical, and malignant variants. We sought to validate and extend these findings in a larger series of well-characterized OFMT, in particular malignant variants. Slides and blocks from 41 OFMT were retrieved, rereviewed, and classified as typical, atypical, and malignant using previously published criteria. Interphase fluorescence in situ hybridization (FISH) was performed on paraffin-embedded sections of each case using a break-apart probe strategy, with direct-labeled FISH probes designed from bacterial artificial chromosomes. The 41 tumors occurred in 23 men and 18 women with a mean age of 55 years and involved the head and neck, trunk, and upper and lower limbs. The tumors were classified as typical (n=14), atypical (n=6) and malignant (n=21). PHF1 rearrangements were detected in 20 of 41 cases (49%) including 43% typical, 50% atypical, and 52% malignant cases. The results of our study confirm previous findings, with PHF1 rearrangements present in nearly 50% of OFMT, including roughly similar percentages of typical, atypical, and malignant tumors. These results support our previous hypothesis that OFMT might represent a translocation-associated tumor, underscore the likely importance of PHF1 rearrangements in the pathogenesis of these lesions, confirm the relationship between typical and malignant OFMT, and suggest a role for PHF1 FISH in the diagnosis of morphologically challenging cases.