Based on both morphological and physiological traits, Asian cultivated rice (Oryza sativa L.) can be classified into two distinct subspecies, indica and japonica. To better understand the differences between the two subspecies, a proteomic approach was used to profile proteins present in the yellow seedling stage of 10 indica and 10 japonica rice varieties. We report the discovery of a new protein, Indica Special Protein (ISP), which was only detected in yellow seedlings of indica varieties, and was absent from japonica varieties. Hence, ISP may represent a key gene for the differentiation of indica and japonica subspecies.