An unusual case of triple location (skull, patella and thigh) Cryptococcus neoformans is described. The peculiarity of the case is based on the probability of direct post-traumatic bone inoculation, subsequent seeding from skull to patella, thigh and cerebral spinal fluid (CSF), patella involvement, lack of evidence of lung involvement and lack of predisposing underlying disease. The response to surgery and a combination of amphotericin B and 5-flucytosine administration was favorable without relapse at follow-up after 7-year discontinuation of therapy.