Digital cancer diagnosis is a research realm where signal processing techniques are used to analyze and to classify color histopathology images. Different from grayscale image analysis of magnetic resonance imaging or X-ray, colors in histopathology images convey large amount of histological information and thus play significant role in cancer diagnosis. Though color information is widely used in histopathology works, as today, there is few study on color model selections for feature extraction in cancer diagnosis schemes. This paper addresses the problem of color space selection for digital cancer classification using H and E stained images, and investigates the effectiveness of various color models (RGB, HSV, CIE L*a*b*, and stain-dependent H and E decomposition model) in breast cancer diagnosis. Particularly, we build a diagnosis framework as a comparison benchmark and take specific concerns of medical decision systems into account in evaluation. The evaluation methodologies include feature discriminate power evaluation and final diagnosis performance comparison. Experimentation on a publicly accessible histopathology image set suggests that the H and E decomposition model outperforms other assessed color spaces. For reasons behind various performance of color spaces, our analysis via mutual information estimation demonstrates that color components in the H and E model are less dependent, and thus most feature discriminate power is collected in one channel instead of spreading out among channels in other color spaces.