A 4 mm white lesion resembling candidiasis on the tongue fails to respond to 2 weeks of nystatin therapy. What is the most appropriate next step?

When an oral lesion presumed to be candidiasis does not resolve after appropriate antifungal therapy, a biopsy is mandatory to rule out dysplasia or malignancy — particularly oral squamous cell carcinoma, which can present as a white or mixed red-white lesion. An incisional biopsy (representative tissue sample) is preferred for lesions over 1 cm or when malignancy is suspected. For a 4 mm lesion, excisional biopsy (complete removal) would also be appropriate as it achieves both treatment and diagnosis simultaneously. However, incisional biopsy is the gold standard for any persistent suspicious lesion.