A man anticoagulated with warfarin 57.5 mg/week (international normalized ratio [INR] 1.94) was diagnosed with nonsmall cell lung cancer and prescribed weekly gemcitabine. With the first dose of the first cycle, his INR rose to 3.52, and his weekly warfarin dose was decreased to 52.5 mg. The lower warfarin dose was continued during the 2-week rest period between cycles 1 and 2 of gemcitabine therapy, and his INR decreased to 2.08. The patient resumed gemcitabine while taking warfarin 52.5 mg/week; however, the warfarin dosage had to be reduced to 48.5 mg/week to achieve a therapeutic INR. After gemcitabine was discontinued, the patient was restabilized at the prechemotherapy baseline dosage. We conclude that an interaction between warfarin and gemcitabine occurred with the first dose of the latter and recommend weekly INRs for anticoagulated patients receiving gemcitabine.