Abstract In female squirrel monkeys (Saimiri sciureus), the reproductive period normally extends from ∼2.5 years to the mid-teens. In the present study, we examined the age-associated cytological changes in the ovaries of 24 squirrel monkeys ranging in age from newborn to ∼20 years. We found a significant, age-related decline in the number of primordial follicles, with the most pronounced loss occurring between birth and 5 years. After ∼8 years of age, relatively few primordial follicles were evident in the ovarian sections examined. An unusual feature of the aging squirrel monkey ovary is the emergence of highly differentiated, encapsulated clusters of granulosa cells that increase in size and number, particularly after the age of 8 years. Many of these cells express anti-Müllerian hormone, and, histologically, the clusters resemble granulosa cell tumors in humans. However, granulosa cell clusters (GCCs) are present in both ovaries of all older squirrel monkeys, and they display no obvious signs of malignancy, suggesting that they are a normal feature of ovarian aging in this species. Our findings indicate that reproductive senescence in female squirrel monkeys, as in other primates, involves the inexorable depletion of ovarian follicles. In addition, the consistent appearance of abundant, well-differentiated clusters of granulosa cells in older squirrel monkeys, prior to the cessation of reproduction, suggests that these structures may influence the later stages of reproductive potential in this species. Analysis of GCCs in older squirrel monkeys also could yield insights into the pathophysiology of granulosa cell tumors in humans.