A method and system for classification of cells and particles in a biological sample using an automated image-based feature extraction and classification architecture. A method operates by applying a mask or series of masks to an image, extracting features from the unmasked portions of the image based on the content and location of colored pixels, selecting a subset of the extracted features, and mapping the subset of the extracted features into a classifier architecture. In a majority of cases, the first level model architecture provides an accurate identification of the cell or particle. In a minority of cases, the classification of the cell or particle requires a second level step requiring the use of numerical or categorical values from the first level in combination with a second level model.