The tunica vaginalis is an embryologically derived mesothelium-lined outpouching of the peritoneal cavity, which may develop neoplastic mesothelial proliferations similar to, although much less commonly than, pleural or peritoneal surfaces. We herein report our experience with 12 cases of florid paratesticular mesothelial hyperplasia, highlighting the spectrum of morphologic changes seen and the utility of fluorescence in situ hybridization analysis of homozygous deletion of 9p21 as an adjunct diagnostic tool. All cases were referred because of concern regarding the nature of the mesothelial proliferation. The median age of patients at presentation was 44.5 years (range, 16 to 71 y). Ten of 12 patients clinically presented with hydroceles (2 of which were complicated by infection or hemorrhage), 1 with "paraepididymal cyst" and 1 patient with an epididymal cyst. In contrast to the normal tunica consisting of a thin fibrous wall lined by a monolayer of flattened bland mesothelium and no significant inflammation, all of our cases were characterized by background changes of fibroblastic organization and stromal chronic inflammation. In all cases, the mesothelial proliferation within the fibrous and inflamed stroma was sparse and consisted of linear arrays of widely spaced horizontally orientated simple nonbranching elongated tubules and small solid nests and cords that were well spaced apart. There was an abrupt linear demarcation of tubules at the deep aspect of the fibrous tissue, with no evidence of definite invasion into the submesothelial tissue. Fluorescence in situ hybridization for 9p21 was negative in all 5 cases in which tissue was available for analysis. Nine patients with extended follow-up were alive (median 8 y; range, 1 to 13 y). In summary, the proliferative changes seen in reactive mesothelial hyperplasia associated with hydroceles may be florid and mimic malignant mesothelioma. In particular, the entrapment of isolated mesothelial clusters within deep fibrous tissue may be the cause of significant diagnostic difficulty. There are, however, morphologic clues such as linear arraying of widely spaced architecturally simple cell clusters that may aid in the correct identification of the benignity of these proliferations.