We define comparative disease profile (CDP) as a collection of facts and/or symptoms that are significantly different between a disease group and a user-defined control group. We have developed a computer system that can automatically generate a comparative disease profile from clinical data. It allows the user to explicitly specify the disease group and the control group, and thereby focus attention on differences of interest. The resulting profile can be used in diagnosing new patients. CDFs differ from standard disease profiles which often do not clearly define the reference population against which the profiles are generated. Our system can also automatically diagnose new patients, and allow an optional explanation to be given after each diagnosis. Furthermore, the user can perform sequential diagnosis using the system. We have applied the system in the domains of heart disease, diabetes, and breast cancer to demonstrate its generality and accuracy.