Profundulus mixtlanensis can be diagnosed from other congeners by the following characters: a pronounced lower jaw; 30-35 lateral scales; lack dark body spotting on the posterior half of the body caused by melanization of the base of the scales; in lateral view, dorsal profile of the head shows a concavity just above the supra-occipital crest, which quickly reaches a flat profile posteriorly, an attribute that becomes more pronounced with age; body height <2/3 of SL; pre-pectoral distance <1/3 of SL; distance between ventral and anal fins 15% of SL; caudal peduncle depth 13% of SL; post-anal length 15% of SL; head length 26-28% of SL; preorbital length 26-30% of HL; eye diameter 26-28% of SL; anal-fin length 16-17% of SL; 30-35 lateral scales; 12-21 anal-fin rays; 14-17 pectoral-fin rays (Ref. 106146).