This article describes the first case of a giant pancreatic pseudocyst in a 48-year-old man with HIV infection under combination antiretroviral therapy. The patient presented with an abdominal mass involving the epigastrium, left hypochondrium, and left flank. An enhanced abdominal computed tomography (CT) scan showed a well-defined cyst of 21 cm in diameter, with a liquid content that dislocated adjacent viscera. Microbiological and cytological tests on fluid were negative, confirming diagnosis of pancreatic pseudocyst. The CT-guided percutaneous drainage was carried out and the patient's clinical condition gradually improved.