It is known that, on occasion, histiocytic proliferations can be confused with reactive mesothelial cell hyperplasia or with a malignant process. We report four cases of histiocytic proliferation, two occurring in the pleura in a 23-year-old woman and a 78-year-old woman, respectively, one in a hernial sac of a 2-year-old boy, and one in the lamina propria of the bladder of a 74-year-old man with a noninvasive papillary transitional cell carcinoma. The morphologic features of the pleural lesion of the 23-year-old woman and of the hernial sac lesion of the 2-year-old boy, as well as the bladder lesion, were similar to those reported in cases of the so-called nodular mesothelial hyperplasia. The pleural lesion in the 78-year-old woman consisted of a proliferation of cells with a signet ring-like morphology that was originally interpreted as either an unusual form of mesothelial hyperplasia or a metastatic signet ring cell adenocarcinoma. Because of mitotic activity and some cellular atypia in the bladder lesion, the possibility of invasive transitional cell carcinoma into the lamina propria was considered before immunohistochemical studies were performed. Staining for keratin showed only a few positive cells in the hernial sac and pleural lesions, whereas most cells reacted for the histiocytic marker CD68. Immunohistochemical studies on the bladder lesion also demonstrated strong staining for CD68, but no reactivity for keratin was observed. Based on these results, it is concluded that all of the lesions are primarily reactive histiocytic proliferations and because they may occur in other locations aside from the serosal membranes, the designation "nodular histiocytic hyperplasia" appears to be more appropriate than that of nodular mesothelial hyperplasia. It is important that the reactive nature of these lesions be recognized because on occasion they may present high mitotic activity or may show signet ring-like morphology and thus they can be confused with a malignancy.