Testicular regression syndrome (TRS) represents a congenital condition in which no normal testicular tissue can be identified following exploration for a clinically impalpable testis. A spectrum of pathological findings may be present but there is little literature systematically examining these features. We searched a pediatric histopathology database to identify cases of TRS, and the histopathological findings were reviewed and pooled with those of all previously published smaller series. A total of 117 cases were identified during the period (1989-2004), median age 2 (range birth-12) years. In 52 (44%) a nodule was identified macroscopically, median maximum diameter 0.5 (range 0.1-2.0) cm. Microscopic hemosiderin-laden macrophages were present in 85 (73%), dystrophic calcification in 52 (44%), residual testicular tubules in 12 (10%), vas deferens in 71 (61%), and epididymal tissue in 39 (33%). The prevalence of hemosiderin laden macrophages and dystrophic calcification were significantly greater in cases < or =3 years (84% versus 64% and 55% versus 32%, respectively). But there was no significant difference in the frequency of other findings between the younger and older age groups; in particular, the presence of residual testicular tubules was similar (7% versus 13%, respectively). Furthermore, there was no significant correlation between identification of a macroscopically distinct nodule and presence of residual tubular structures, tubules being identified in 6 of the 65 cases in which no clearly identifiable nodule was seen macroscopically. The presence of hemosiderin-laden macrophages and foci of dystrophic calcification showed a positive association. TRS is associated with specific histopathological features, the findings being consistent with changes secondary to intrauterine testicular torsion. Residual testicular tubules are found in 10% of cases regardless of the presence or absence of a macroscopically identifiable nodule.