Oral soft tissue diseases present a diverse array of conditions that often share similar clinical characteristics, making precise diagnosis dependent on both clinical skills and appropriate supplementary investigations. Diagnostic procedures are essential for differentiating benign, reactive, inflammatory, and malignant lesions. These methods include histopathological examination, cytological analysis, microbiological cultures, serological testing, molecular diagnostics, and direct immunofluorescence. Each technique delivers unique insights into the underlying nature of the disease. This chapter explores these diagnostic tests as they pertain to oral soft tissue diseases.