Background Salivary tumors have various morphological features and might share some histopathological findings. They are considered a problematic area in diagnosis due to complex clinicopathological features and different biological behavior. Objective To identify the pathological behavior of salivary tumors immunohistochemically. Methodology This retrospective study involved thirty formalin-fixed paraffin-embedded blocks of salivary gland tumors. These tumors were stained immunohistochemically with syndecan-1 and cyclin D1. Chi-Square test was used to relate immunoscoring, intracellular localization, intensity, and invasion to different salivary tumors. The correlation of these two markers was done by spearman‘s rho test. P-value <0.05 was considered statistically significant. Results The mean age of the patients was 48.69 ± 17.7. The parotid gland was the most commonly reported site in benign tumors, and regarding malignant tumors, maxilla was the most prevalent site. Syndecan-1 in benign tumors showed a predominate score 3, most widely detected in pleomorphic adenoma. Malignant salivary tumors showed 89.4% positive expression with a more frequent score 3, most commonly found in adenocystic carcinoma. Cyclin D1 expressed in all benign salivary tumors, with prominent diffuse mixed intracellular localization in pleomorphic adenoma. Malignant tumors revealed an expression of 94.7%. Moderate scoring with mixed intracellular localization was recorded in adenocystic carcinoma, followed by mucoepidermoid carcinoma. There was a significant correlation between the two markers in response to the distribution of immunostaining in different cell compartments. Conclusion Syndecan-1 and cyclin D1 showed a significant combined role in salivary tumor progression. Interestingly notable ductal-myoepithelial cells affect epithelial morphogenesis, and growth of pleomorphic adenoma was observed. Furthermore, basophilic cells of cribriform adenocystic carcinomas might control the aggressiveness and proliferation rate of these tumors.

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