Stiff-person syndrome (SPS) is a rare disorder that affects the central nervous system, being characterized by intermittent episodes of muscle spasms, rigidity, and a significant increase in morbidity and mortality. We report a 29-year-old patient, with left-sided chylothorax and thymoma, who presented with truncal, lower extremities stiffness and painful cramps alleviated by diazepam and ... [Show full abstract] opiates. His clinical picture was suggestive of SPS secondary to invasive thymoma. This syndrome is best approached by its early recognition and prompt treatment since a missed diagnosis can have deleterious outcome. An intensive search for the underlying etiology is of utmost importance in the management of SPS. A review of the current literature is also included in this manuscript.