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To date, there is no reliable biomarker validated in the exploration of nasopharyngeal cancer (NPC). To assess the value of 2 markers: Cyfra 21-1, a fragment of cytokeratin 19, and beta2Microglobulin, a cell membrane protein, in CNP in southern Tunisia, we included 103 individuals: 50 patients with a primary diagnosis of CNP and 53 healthy controls. CNP patients were classified according to the American Joint Committee on Cancer (AJCC 2010) and the 8th edition TNM (UICC 2017). 40/50 (80%) of CNP patients were positive for at least one of the two markers. The mean serum level of Cyfra 21-1 was significantly higher in patients than in controls. None of the controls had an elevated level of this marker. The sensitivity of Cyfra 21-1 in CNP (66%) reached 100% for patients <30 years of age. Cyfra 21-1 levels were significantly correlated with advanced stages ( III). Regarding beta2M, 56% of patients had an elevated level of the marker. In conclusion, Cyfra 21-1 could be a reliable biomarker for the diagnosis and prognosis of NPC. Combining this marker with beta2M could improve diagnostic sensitivity.