Fragilaria mesolepta differs from F. subconstricta, F. tenuistriata, and F. capucina by the shape of the apices and the shape of the center of the valves. The apices of F. mesolepta are rostrate to subcapitate, while the apices are broadly rounded in F. subconstricta and rostrate in F. tenuistriata. Valves of F. mesolepta are constricted in the center, while the other taxa are nearly linear.