The authors have presented what they believe is the only reported case of a stress fracture of the tarsal middle cuneiform bone. Stress fracture pathogenesis, as well as diagnosis and treatment, were reviewed. It has been proposed that the middle cuneiform may be subject to increased stress in the runner during the propulsive phase, as this is the midfoot bone that transmits weight proximally in the medial column. This is evident by studying the cancellous structure of the tarsal bones. The ligamentous and osseous architecture of this region also can produce a midfoot buckling when the foot is plantarflexed against resistance. Prompt diagnosis and treatment is the key in preventing the stress fracture from becoming a chronic source of discomfort.