Cryptococcus neoformans is an encapsulated, yeast-like fungus that can cause a systemic mycosis, particularly in immunocompromised patients. Disseminated infections typically affect the central nervous system, and osseous lesions are infrequent. Only 5%-10% of disseminated cryptococcosis involves bones. A 69-year-old female presented pain, swelling, and a soft tissue mass in her right lateral hindfoot. Her medical history included a kidney transplant (10 years earlier) secondary to chronic disease due to IgA nephropathy. The patient underwent an excisional biopsy, surgical debridement, and secondarily negative pressure wound therapy to achieve skin closure. Biopsy revealed a rare Cryptococcus neoformans osteomyelitis of the calcaneus. The patient then received IV treatment with liposomal amphotericin B at 3 mg/kg/d for 25 days. In conclusion, we present a case of cryptococcal osteomyelitis which, although not a frequent disease, must be considered as one of the differential diagnoses of osteolytic osseous lesions in patients with chronic osteomyelitis. Cryptococcus neoformans may be a potential cause of below-knee infection, mainly in immunocompromised patients.