Background: Salivary gland lesions show wide morphological diversity making accurate diagnosis challenging. Fine needle aspiration cytology (FNAC) is a widely used initial diagnostic tool and its accuracy can be improved by histopathology and immunohistochemistry (IHC). Objectives: To evaluate the diagnostic accuracy of FNAC in salivary gland lesions by correlating cytological findings with histopathology and immunohistochemical interpretations. Methods: This prospective study was done at a tertiary care center in 50 cases of major and minor salivary gland lesions evaluated by FNAC and corresponding histopathology followed by immunohistochemistry which was performed in selected cases using markers such as p63, S100, CD117, EMA, SMA, DOG1, and HER2/neu. Results: FNAC demonstrated a sensitivity of 83.3%, specificity of 64.3%, and overall diagnostic accuracy of 78%. FNAC showed good correlation with histopathology for common benign tumors, while differences were noted in cystic, inflammatory and low-grade malignant lesions. Immunohistochemistry aids in diagnosing difficult cases with better accuracy. Conclusion: FNAC is an effective first line diagnostic modality for salivary gland lesions. The combined use of FNAC, histopathology and immunohistochemistry significantly enhances diagnostic accuracy particularly in lesions with overlapping cytomorphological features.

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