Profundulus portillorum belongs to the P. labialis species group and can be distinguished from its congeners by having a smaller eye and fewer anal and pectoral-fin rays. Eye diameter typically less than one fourth of the head length (greater than 25% in all other Profundulus), 12 anal fin rays modally (≥ 13 in all other Profundulus), 14 pectoral-fin rays modally (≥ 15 in all other Profundulus). It differs from P. guatemalensis, P. oaxacae and P. punctatus by the absence of a humeral spot and by having less than half of the basal portion of the caudal fin densely covered by scales. It is distinguished from P. hildebrandi and P. labialis by having <35 lateral-line scales and from P. candalarius by having a shorter body depth (Ref. 84033).