Methods and systems for selecting defect detection methods for inspection of a specimen are provided. One system includes one or more computer subsystems configured for separating polygons in a care area into initial sub-groups based on a characteristic of the polygons on the specimen and determining a characteristic of noise in output generated by a detector of an inspection subsystem for the polygons in the different initial sub-groups. The computer subsystem(s) are also configured for determining final sub-groups for the polygons by combining any two or more of the different initial sub-groups having substantially the same values of the characteristic of the noise. In addition, the computer subsystem(s) are configured for selecting first and second defect detection methods for application to the output generated by the detector of the inspection subsystem during inspection of the specimen or another specimen.