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Pseudoangiomatous stromal hyperplasia (PASH) is frequently a microscopic incidental finding in breast biopsies performed for benign or malignant disease. However, it may also produce a mass lesion. We reviewed PASH seen first as a tumor in 40 women aged 14 to 67 years (mean, 37 years). All but one lesion were clinically palpable. The exceptional tumor was found by mammography. The mass, typically unilateral, was usually diagnosed clinically as a fibroadenoma. Most specimens contained a well-circumscribed tumor with a firm white-gray cut surface. In six cases, there was no discrete gross lesion in the surgical specimen. Microscopically, there was a spectrum of pathological stromal changes ranging from classical PASH with anastomosing slit-shaped spaces outlined by flat, bland spindle cells to more proliferative lesions composed of bundles of plump spindle cells that obscured the underlying pseudoangiomatous architecture in the most florid lesions. The spindle cells were vimentin and CD34 positive and factor VIII negative. In more cellular fascicular lesions, the stromal cells acquired desmin and actin positivity. These immunohistochemical features were consistent with myofibroblastic histogenesis of PASH. Reactivity for progesterone receptor (PR) typically exceeded estrogen receptor (ER) in the nuclei of stromal and glandular cells. In most lesions, the nuclei of stromal spindle cells were ER negative. The majority of the patients were treated by excisional biopsy. One lesion, incompletely excised, spontaneously regressed. One patient had bilateral mastectomies. Follow-up was 0.6–11 years (mean, 4.5 years). Five patients had ipsilateral recurrences, and two had subsequent contralateral PASH. The morphological spectrum of cellular proliferation and staining qualities indicates that the myofibroblast plays a major role in the histogenesis of PASH. The pathogenesis of PASH remains uncertain, but aberrant reactivity of myofibroblasts to endogenous or exogenous hormones is likely to be an important factor. Simple excision is adequate treatment initially and for infrequent recurrences. Diffuse PASH occasionally presents a difficult management problem that may necessitate mastectomy.