The authors describe an evidence-based assessment protocol for intensive case management to improve screening diagnostic follow-up developed through a research project in breast and cervical cancer early detection funded by the Centers for Disease Control and Prevention. Three components of an evidence-based approach to assessment are presented and illustrated in the Screening Adherence Follow-up (SAFe) protocol: (1) evidence for known risks and barriers for the target population; (2) standardized assessment elements; (3) evidence for the accuracy, efficiency, and validity of the protocol in use. Testing of the assessment tool in a pilot study of more than 600 women demonstrated practical utility in matching assessed needs with service intensity and confirmed that differential amounts of service and different provider effort achieved equally satisfactory adherence results. The evidence-based components described and the types and nature of evidence on which they draw can be generalized to new settings and client concerns.