Four cases with native pulmonary muscular proliferation (NPMP) are reported. The etiology of this rare condition is unknown. A hamartomatous process is discussed. In spite of its rarity the correct diagnosis of this condition is important. Both clinically and histologically in transbronchial biopsies, NPMP may be mistaken for pulmonary lymphangioleiomyomatosis (PLAM). Distinction of these 2 conditions is adamant, as PLAM has a poor prognosis, and, moreover may be associated with general disease, as with tuberous sclerosis. Whereas the typical distribution of more mature desmin positive muscle cells in a dense center core and more immature desmin negative radiating peripheral muscle cell proliferation with fascicular pattern in NPMP may be recognized in open lung biopsy, these differences may not become evident in small transbronchial biopsies. Immunohistochemical methods play an important role in the differential diagnosis--as with PLAM estrogen and progesterone receptors may be expressed and, most importantly, the reaction of the HMB45-antibody appears consistently positive in muscle cells of PLAM, while negative with NPMP. Thus, recognition of this clinically innocent disease is also possible in small tissue particles.