We investigated changes in the incidence of amyotrophic lateral sclerosis (ALS) in the Koza/Kozagawa/Kushimoto area (K. area) in the Kii Peninsula, Japan in 1960-2009. Probable and definite ALS cases diagnosed using El Escorial criteria were collected during a five-decade period: period I-V, 1960-2009. Forty-three ALS patients matched the selection criteria in the overall K. area, including three patients on Oshima, a small island opposite the mainland K. area. The age- and gender-adjusted incidence of ALS in the overall K. area (standardized for the 2005 Japanese population) decreased from 5.47/100,000 (95% CI 1.86-9.08) in period I to 0.61/100,000 (95% CI-0.28-1.50) in period III, and then increased to 4.39/100,000 (95% CI 1.70-7.07) in period V. On Oshima, the age- and gender-adjusted incidence of ALS was 9.45/100,000 (95% CI-7.39-26.29) in period V. The present research indicates an increase of ALS incidence in the K. area, especially on Oshima. A limitation of this study was the small population.