Flavobacterium columnare (F. columnare), the dermotropic Gram negative yellow pigmented bacteria was isolated from different sites of skin ulcerations in the Nile tilapia (Oreochromis niloticus) and Nile catfish (Clarias gariepinus) collected from an earthen pond located at an aquaculture station in Sharkiya Province, Lower Egypt during an acute episode of mass kills during the early summer of 2009. An acute infection with F. columnare was behind the emergent event of mass mortalities among both populations. Many of the Nile tilapias exhibited typical signs of hole - in- the head like lesions from which F. columnare together with the myxosporean spore, Myxobolus tilapiae (M. tilapiae) were retrieved. Most of the cohabitating infected Nile catfishes exhibited severe form of saddle back like ulcer. The identities of the retrieved isolates were confirmed using morphological, biochemical and molecular tools. The research lead us to conclude that the two diverse etiological agents (F. columnare and M. tilapiae) under the triggering effect of the abrupt change in the water quality measures (abrupt rise in the water temperature, ammonia, pH, sharp decrease in dissolved oxygen) have synergized together to induce the above mentioned pathology with the consequent reemergence of fish mass mortalities.