The gross morphology and histopathology of lesions formed in “hole-in-the-head” disease, commonly found in cichlids, is described in the Nile Tilapia, Oreochromis niloticus. The most severe lesions, which in some fish extended into the lateral line canals, were found posterior to the eye. In histological sections of this region in fish without lesions, we found previously unreported small canals running parallel to the epidermis, opening at the surface through pores. These canals arose from the lateral line canals, and may provide an entry route for pathogens and toxins, which could infiltrate into surrounding tissues through the simple epithelium lining the canals. We found most lesioned fish in crowded tanks, where aggressive behavior and poor water quality would damage and stress the fish. Bacteria were seen in these lesions, but we did not find flagellates, which have been implicated in this disease in other cichlids.