Macrodystrophia lipomatosa (MDL) is a rare, congenital, developmental anomaly causing localized overgrowth of a digit(s) or extremity. Trigger wrist is a relatively rare entity, which may be caused by a mass originating from a tendon, an anomalous muscle or intracarpal pathologies. A 42-year-old male patient presented with triggering during active motion of the fingers and intractable pain and numbness in fingers to our emergency department. He had hypertrophy of the entire right upper extremity and his huge thumb was amputated due to MDL four years ago. The index finger was bigger than the other fingers and thenar eminence area of the hand looked like a large mass. Resection of hypertrophic carpal bone and debulking of large soft tissue mass removed the carpal tunnel symptoms and limited the range of motion of the wrist and fingers. This is a case report of triggering at the wrist and severe carpal tunnel syndrome due to carpal bone enlargement and lipofibromatous hamartoma (LH) of the median nerve in a patient with MDL.