In severe cases of denture stomatitis, antifungal drugs are sometimes ineffective. This case is a 72-year-old patient who was prescribed fluconazole for five months but had no improvement in symptoms. After re-diagnosis, medication was performed, and temporary dentures were fabricated for oral rehabilitation. This report describes that microbiological analysis and adjuvant therapy can be helpful, in case does not improve symptoms even with continuous medication of antifungal agent.