Fat distribution disorders are among the most frequent side effects of antiretroviral treatment. The pathophysiologic mechanism(s) for these events remains unclear, and a casual link to a specific drug or class of drugs is uncertain. The physical changes associated with the lipodystrophy syndrome can be divided into three major types: lipoatrophy or fat wasting; lipohypertrophy or fat accumulation; and mixed forms with atrophy and hypertrophy coexisting in different body regions. Fat accumulation can occur in one or more of several areas including dorsal-cervical and abdominal regions and breasts. Withdrawal of antiretroviral therapy does not seem to influence the stabilized lesions significantly, and no one of the therapeutic strategies adopted so far was capable to achieve substantial improvements. Here we describe the successful and lasting treatment of a massive and movement/posture-hampering breast hypertrophy with reductive mastoplasty.