Among cocaine addicts, there is a strong variation in response to relapse provoking factors like conditioned cues and renewed contact with the drug. Here we show that such large individual differences also exist in rats. Reinstatement of extinguished cocaine-seeking behavior was triggered by contingent presentation of a cocaine-conditioned cue or an amphetamine priming injection. We found no positive correlation between cue- and drug-controlled reinstatement of cocaine seeking. Rather, a slight, but significant negative correlation was observed, which was particularly evident in two subgroups of rats that responded highest following either amphetamine priming or cue presentation. A large middle group responded equally for both relapse provoking factors. Further, cocaine-seeking behavior during the first extinction session correlated positively with cue-induced reinstatement. In conclusion, the present findings indicate that the therapeutic efficacy of relapse prevention strategies may depend on individual sensitivity to distinct relapse provoking stimuli.