We report the case of a patient with acute lymphoblastic leukemia who developed a secondary Philadelphia chromosome-positive clone (Ph(+)). Although the Ph was not detected at diagnosis with conventional cytogenetic analysis and with molecular methods (reverse transcriptase polymerase chain reaction), the Ph was detected with the same techniques at relapse. This anomaly is usually related to the initiation of the disease, but can be a late event related to progression. We discuss these hypotheses and review the literature.