Rationale. Induction of apoptosis in sensitive tumor cells is the main mechanism of action of chemotherapy agents in human cancers. Also, the assessment of drug-induced apoptosis soon after chemotherapy may be an early predictor of treatment efficacy. Patients and Methods. A phase I/II study was prospectively conducted in 15 patients presenting with proven lung cancers (n = 10), breast cancers (n = 2), and lymphomas (n = 3) to assess the value of the Tc-99m-radiolabeled recombinant human (rh) Annexin V for imaging apoptosis immediately after completion of the first course of chemotherapy. Early Annexin V findings post-chemotherapy (day+1, day+2) were also compared to the tumor status at 6 to 12 weeks post-treatment. Results. All lung and lymphoma patients with an increased tracer uptake post-treatment (n = 8) had either partial or complete tumor response. Five patients with no tracer uptake had progressive disease. However, two breast cancers had a response to treatment, although no significant tracer uptake was observed. Tumor response and survival time were significantly correlated with the Tc-99m-labeled Annexin V uptake. No serious events related to tracer administration were noted. Conclusion. Preliminary results of this pilot study demonstrate the feasibility of the Tc-99m-labeled Annexin V uptake for the in vivo imaging of apoptosis after one course of chemotherapy. If confirmed on larger series, these promising results may open new perspectives in the management of oncology patients.