The piriformis muscle is a critical lateral rotator of the hip and an important anatomical structure due to its proximity to the sciatic nerve and sacral plexus. Agenesis of the piriformis muscle is a rare anatomical variant, with very few cases of unilateral agenesis reported in the literature. To the authors' knowledge, bilateral piriformis agenesis has not been previously documented. This report presents two cases of piriformis agenesis: one unilateral and one bilateral. The clinical implications of piriformis agenesis remain unclear, as its contribution to symptoms such as back or gluteal pain is not well understood. Moreover, its rare occurrence suggests it may often be under-recognized, potentially leading to misdiagnosis or missed diagnoses. Awareness of this anatomical variation is crucial, particularly for interventions in the deep gluteal region, where the piriformis muscle serves as an important anatomical landmark. This report emphasizes the importance of recognizing piriformis agenesis.