This study examined the efficacy of doxorubicin-based chemotherapy used for rescue therapy in refractory feline lymphoma. Records of 23 cats with lymphoma treated with chemotherapy who received doxorubicin for the first time in a rescue setting were reviewed. Seventeen (74%) of the 23 cats had only one treatment of doxorubicin. Five (22%) of the 23 cats had a positive response to doxorubicin and were given additional doses. The response to therapy in 4/5 of these responders could be assessed objectively, of which, two cats (9%) achieved partial remission (PR) and two cats (9%) achieved complete remission (CR). The two cats that achieved CR had differing response durations (6 weeks and greater than 47 months). Three of these five (60%) responders had also received concurrent other chemotherapy in addition to doxorubicin. Cell type and the use of concurrent chemotherapy were significant predictors of response. Cats with small-medium cell lymphomas (P=0.001) and cats that received concurrent chemotherapy with doxorubicin rescue (P=0.007) were more likely to respond favorably. This study suggests that doxorubicin-based chemotherapy is not an effective rescue protocol for feline lymphoma.