Despite the Entamoeba histolytica was first discovered more than 160 years ago, it remains a major health problem in developing countries, including Egypt. Discriminating the morphologically similar pathogenic species from the non-pathogenic one is a challenging task, specifically when relying on the traditional diagnostic tools as microscopy. The objective of the current study was to assess the usefulness of detecting E. histolytica coproantigen and specific salivary IgA for proper identification of intestinal infection with E. histolytica, using ELISA, in relation to the gold standard realtime PCR technique. 38 stool samples were proved positive for E. histolyticalike stages by microscopy and subsequently exposed to molecular analysis, using specific primers and probes related to E. histolytica which excluded 8 out of these 38 samples, indicating their relation to non-pathogenic species. All diagnostic tests achieved 100% specificity and relatively good sensitivity of 93.3 and 86.6% for specific coproantigen and salivary IgA respectively. Conclusively, ELISA-specific coproantigen or secretory salivary IgA are rapid reliable cost-effective and relatively sensitive diagnostic tools that can discriminate between pathogenic E. histolytica from those of non-pathogenic E. dispar, thus helpful in epidemiological surveys. The short duration of the secretory IgA may pose additional advantages as it can diagnose active infection, besides its ability to diagnose amoebic liver abscess.