Background: Nasopharyngeal carcinoma (NPC), particularly the non-keratinizing subtype (NK-NPC), is prevalent in Southeast Asia and often presents diagnostic challenges due to overlapping histological features with benign nasopharyngeal lesions. While Epstein–Barr virus (EBV) serology supports diagnosis in many cases, its limitations in sensitivity and specificity necessitate additional tissue-based markers. Objective: To assess the immunohistochemical expression of cytokeratins CK8/18 and CK19 in NPC compared to benign nasal tissue and evaluate their potential as adjunct immunohistochemical markers. Methods: This retrospective study evaluated the immunohistochemical expression of cytokeratins CK8/18 and CK19 in 24 NK-NPC and 22 benign nasopharyngeal tissue samples collected between April 2021 and April 2024 at Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia. Staining intensity and distribution were scored semi-quantitatively, and statistical analysis was performed using SPSS v29.0 (p < 0.05). Results: CK19 was expressed in all NK-NPC cases, with strong positivity in 79.2%, while CK8/18 was positive in 92%, primarily with weak to moderate staining. Only one benign case (inverted papilloma) showed focal positivity. The differences in expression between malignant and benign tissues were statistically significant (p < 0.001). Sub-analysis of EBER-positive cases (n = 15) confirmed consistently strong CK19 expression. Conclusions: Based on this small retrospective cohort, CK8/18 and particularly CK19 demonstrate expression patterns that may support their use as adjunct immunohistochemical markers in the histopathological assessment of NK-NPC, especially in morphologically ambiguous cases. Further validation in larger studies is needed before these markers can be considered for routine diagnostic application.