PEComas (tumors showing perivascular epithelioid cell differentiation) are a family of mesenchymal neoplasms that include angiomyolipoma, clear cell "sugar" tumor of the lung, lymphangiomyomatosis, and a group of uncommon lesions that arise in soft tissue, visceral organs, and skin. We describe a distinctive variant of PEComa that shows extensive stromal hyalinization, a feature not previously described in these tumors. Thirteen PEComas with extensive stromal hyalinization were identified from a total of 70 cases of PEComa received between 1996 and 2006 (19%). All patients were women, with a mean age of 49 years (range, 34 to 73y). One patient had tuberous sclerosis. Ten tumors (77%) arose in the retroperitoneum (8 pararenal), and 1 each in the pelvis, uterus, and abdominal wall. Median tumor size was 9.5 cm (range, 4.5 to 28 cm). All except 2 were grossly well-circumscribed. The tumors were composed of cords and trabeculae of cytologically uniform bland epithelioid cells with palely eosinophilic, granular to clear cytoplasm and round nuclei with small nucleoli, embedded in abundant densely sclerotic stroma. Five tumors contained a spindle cell component, and 6 showed focally sheetlike areas. In all cases the tumor cells were focally arranged around blood vessels. All tumors lacked the delicate nesting vascular pattern typical of other PEComas. Mitoses ranged from 0 to 3/50 high-power field (mean 1) in all cases except 1. One tumor showed abrupt transition to areas with strikingly pleomorphic morphology, marked nuclear atypia, frequent mitoses (22/10 high-power field), and fascicular and nested architecture. This was the only case with necrosis. All tumors were immunopositive for desmin (usually diffusely) and HMB-45 (generally in scattered cells); 12/13 (92%) expressed smooth muscle actin, 11/12 (92%) caldesmon, 11/12 (92%) microphthalmia transcription factor (D5), and 3/13 (23%) melan-A. Only 1 (8%) was focally S-100 positive. All tumors were negative for epithelial membrane antigen, PAN-K, and KIT (CD117). Follow-up was available for 9 patients, ranging from 10 to 64 months (median, 33). One patient (whose tumor showed transition to high-grade malignant morphology) developed metastases to lung, liver, and abdominal wall. No other tumor has recurred or metastasized thus far. Sclerosing PEComa is a distinctive variant with a predilection for the pararenal retroperitoneum of middle-aged women. Sclerosing PEComas seem to pursue an indolent clinical course, unless associated with a frankly malignant component. Long-term follow-up will be required to confirm these findings.