Malignant phyllodes tumors of the breast are aggressive, occurring less frequently than fibroadenomas. The diagnosis is established after excluding metaplastic carcinoma and sarcomas. A 47 year old woman presented a primary tumor composed of hyperplastic epithelial and mucoid component, typically seen in fibroadenomas. Further investigations revealed PanCK, EMA and CK8/18 stained epithelial cells, stromal cells were positive for CD34, weak expression of SMA and CD10; calponin, S100, and p63 negative. Two years after resection, a new mass reappeared in the same breast mainly composed by spindle cells expressed strongly for CD10, SMA, Calponin, Vimentin, CD117, and EGFR, conversely, CD34 and epithelial markers were negative. These features bring into account of mammary not-otherwise specified-type sarcoma with CD10 expression along with myoepithelial features. After extensive sampling, a focal epithelial component was observed. Further comparative genome hybridization revealed similar LOH between both neoplasms, which prompts the possible transformation into amalignant tumor. Among chromosomal alterations, 1q is associated with the malignancy and recurrence. We illustrate the first malignant phyllodes tumor with myoepithelial phenotype that progressed from fibroadenoma. It possibly sheds light on a variant of this disease. Extensive sampling and molecular analysis might assist in the differential diagnosis with NOSCD10 sarcomas with myoepithelial phenotype expression.