The acronym MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) belies the true scope of one of the most prevalent mitochondriopathies in adults. While the original description focused on neuromuscular symptoms, we now recognize this syndrome as genetically well defined but phenotypically profoundly heterogeneous, as exemplified by our experience. Here we report the case of a man who initially presented in 1986. In hindsight, his was a classic manifestation of MELAS, but the illness was ascribed to an ill-defined viral encephalitis. Over the years, diabetes and hearing impairment developed and his functional status deteriorated progressively. It took the quarter of a century to arrive at the correct diagnosis. It is worthwhile to keep an open mind when dealing with chronically ill patients with a seemingly clear-cut diagnosis.