Background: The purpose of this case report was to report a case of Cryptococcus laurentii infection in the left knee of a previously healthy 29 year old male patient. Case presentation: After an initial misdiagnosis and 7 months of failed treatment, the patient received nearly a month of treatment with voriconazole (200 mg IV q12 h) and knee irrigation with amphotericin B until the infection was controlled. The treatment continued with fluconazole for nearly 7 months and approximately 5 weeks of antibiotic treatment for a skin bacterial coinfection. In the end, the patient's symptoms disappeared completely, the left knee recovered well, and there was no recurrence of infection. Conclusion: The key points of successful treatment in this case were the thorough debridement, the adequate course of knee irrigation with antifungal drugs and more than 6 months of oral antifungal drugs that were able to eradicate the infection. © 2020 The Author(s).