Oral cancer is the leading cause of death worldwide and it is the eighth most common cause of cancer death. Cancer cells utilize more glucose and amino acids than their benign counterparts. Diagnosis of disease via the analysis of saliva is potentially valuable, as the collection of fluid is associated with fewer compliance problems than the collection of blood. Hence, the present study was undertaken to evaluate the comprehensive amino acid profiling of saliva by high performance liquid chromatography (HPLC). The study group comprised 16 subjects, of whom eight were classified as having well-differentiated oral squamous (OSCC) cell carcinoma (Group I) and eight were classified as having moderately differentiated oral squamous cell carcinoma (Group II). Eight healthy individuals comprised the control group (Group III). The results showed increased salivary levels of all the amino acids in both groups of OSCC patients (Groups I and II) when compared with healthy controls (Group III). Hence, our study showed higher levels of all amino acids in the saliva of OSCC patients than in the saliva of healthy controls. The increased levels may serve as a "diagnostic and prognostic marker" for oral squamous cell carcinoma and for further detection of metastatic spread.