Aim: Attempts have been made to use CTC values for interpretation of treatment response and to guide change of chemotherapy by using a static cut-off of 5 CTC to stratify patients in favourable or unfavourable responders. We propose a newapproach to interpret treatment effect using significant changes in CTCvalues (SCV-limits 1) asgrouping parameter for responders and non-responders to chemotherapy among metastatic breast cancer (mBC) patients. Method: CTC were analysed using the CellSearch System in blood from 47 mBC patients before the start of new chemotherapy and before the third cycle of therapy. The new and old approach to interpret changes in CTC values were compared in relation to progression free survival (PFS). Results: The new approach using significant CTC change (P =.032) and the old approach using static cut-off (P N.001) correlated significantly with PFS using a cohort of 47 patients. Conclusion: We propose a new approach to interpret significant changes between baseline and follow-up CTC values as a tool for assessing treatment effect in mBC. Our approach stratified patients in new risk groups that were stratified significantly with respect to PFS. More patients are needed to balance the size of the risk groups for better comparison to the existing approach based on a 5 CTC cut-off.