Background and Objectives: Tongue lesions encompass a broad histopathological spectrum ranging from benign reactive conditions to oral potentially malignant disorders and invasive malignancies. This study aimed to characterize the histopathological distribution of biopsy-confirmed tongue lesions and examine clinicodemographic associations with malignant histopathology. Materials and Methods: This retrospective archive-based study included 624 tongue biopsy specimens from unique patients referred to an oral pathology laboratory between 2010 and 2025. Histopathological diagnoses were evaluated according to age and anatomical subsite. Multivariable logistic regression was used to examine associations with malignant histopathology. Results: The median patient age was 50 years (IQR, 37–60), and 54.0% were female. The lateral border was the most frequent biopsy site (53.5%). The most common diagnoses were irritation fibroma (10.6%), papillomatous lesion (10.1%), squamous cell carcinoma (9.6%), hyperkeratosis (9.5%), and moderate epithelial dysplasia (8.3%). Malignant neoplasms accounted for 12.0% of lesions and were most frequent among patients aged ≥65 years (23.7%). Increasing age (aOR, 1.04 per year; 95% CI, 1.02–1.06; p < 0.001) and lateral border localization (aOR, 6.28; 95% CI, 3.14–12.57; p < 0.001) were independently associated with malignant histopathology. Conclusions: Irritation fibroma was the most frequent diagnosis, and the lateral border was the most frequently biopsied site. Clinicopathological patterns varied by age and anatomical subsite, while malignant histopathology was more frequent among older patients and lesions involving the lateral tongue. These findings support careful assessment of suspicious tongue lesions but should not be generalized to malignancy risk in the general population.
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