A healthy 27-year-old woman presented, four months after childbirth, ingravescent pain and claudication of the left lower limb. Magnetic Resonance Imaging of the lumbosacral and iliac regions showed widespread muscular-skeletal lesions. The patient underwent surgery; Cryptococcus neoformans was isolated from surgical samples. Liposomal amphotericin B, fluconazole and itraconazole were administered. Laboratory findings showed lymphocytopenia, with reduction of CD4+ lymphocytes (23 cells per cubic millimeter) in the absence of HIV infection and any other defined immunodeficiency. This is a rare case of muscular-skeletal cryptococcal infection isolated in a subject affected with idiopathic CD4+ lymphocytopenia.