The PHF1 protein is known to affect processes, such as development and cell proliferation, through modulation of histone H3 methylation. Endometrial stromal tumors (ESTs) are the second most common pure mesenchymal tumors of the uterus. ESTs may pose diagnostic challenges particularly when they exhibit variant histologic appearances, involve extrauterine sites, or present as metastatic disease. Several rearrangements involving the genes JAZF1, PHF1, or YWHAE have been identified in ESTs, detection of which may be helpful in the differential diagnosis of these tumors. PHF1 rearrangements were found to occur in endometrial stromal sarcomas but not in endometrial stromal nodules or undifferentiated endometrial sarcomas. Moreover, recurrent rearrangements of the PHF1 gene have also been detected in up to 85% of ossifying fibromyxoid tumors (OFMTs) including benign and malignant cases. Thus, FISH analysis for the detection of PHF1 translocation may also serve as a diagnostic tool to identify OFMT cases.