Automated image analysis methods to identify and quantify tumor buds in a high resolution image of a section of a tumor that is stained using either pan-cytokeratin AE1/3 or hematoxylin and eosin (H&E) are disclosed. The methods may be used to aid and/or replace manual visual inspection for tumor buds and may be used to predict a clinically relevant outcome or treatment in some cases. The disclosed methods may be used for many different cancer types, such as colorectal cancer.