Background Febrile neutropenia (FN) is one of the serious complications of chemotherapy. However, the hematological nadir after chemotherapy and the timing of prophylaxis for FN remain unclear, especially for outpatients. Methods We prospectively analyzed laboratory data from outpatients treated with a single chemotherapy regimen, rituximab (R)-CHOP, on three consultation days (days 8, 10, and 15) after chemotherapy to identify any factors that might predict the onset of the hematological nadir and the optimal timing of G-CSF prophylaxis. Results A total of 100 courses of chemotherapy (total 33 patients) were analyzed. Onset of the hematological nadir was not predictable in any of the patients who had a white blood cell count (WBC) of >5,500 x 10(6)/L and/or monocyte count of >80 x 10(6)/L on day 8, and thus there was little opportunity for G-CSF prophylaxis in each treatment course. Among patients who had a WBC count of 1,500-5,500 x 10(6)/L on day 8, the monocyte count on day 8 was significantly associated with the hematological nadir. Patients who had a monocyte count of <5 x 10(6)/L on day 8, were identified as a high-risk group for neutropenia for whom G-CSF administration during the current treatment course should be considered. Conclusion Our results indicate that, in outpatients receiving R-CHOP chemotherapy, the monocyte count on day 8 is a useful marker of the hematological nadir, allowing an opportunity for G-CSF prophylaxis.