Purpose To evaluate the association in the change of circulating tumor cell (CTC) levels and clinical outcomes (PFS and OS) in patients with advanced non-small cell lung cancer (NSCLC) treated homogenously with docetaxel and gemcitabine administered every 2 weeks. Methods We prospectively evaluated 37 patients for CTC levels at baseline and after 2 months of chemotherapy (before third cycle). Detection was carried out with the CellSearch system. Results Nine of the 37 patients (24 %) had ≥2 CTCs at the baseline determination. Median progression-free survival (PFS) was 4.3 months (95 % CI 2.5–8.3) for patients with CTC 0–1 as compared to 9.4 months (95 % CI 1.2–12.2) for those with CTC ≥2 ( p  = 0.3506). Median overall survival (OS) was 8.1 (95 % CI 2.8–16.3) and 12.2 (95 % CI 1.4–12.2) months for patients with 0–1 CTCs and ≥2 CTCs, respectively ( p  = 0.7639). Patients with a second CTC quantification were classified as: group 1, CTC = 0–1 at baseline and CTC = 0–1 after second chemotherapy cycle (18 patients); group 2, CTC ≥2 at baseline and CTC = 0–1 after second determination (5 patients). Median PFS was 7.7 and 9.9 months for group 1 and group 2, respectively ( p  = 0.4467). Conclusions CTCs ≥2 at baseline were detected only in 24 % of this group of patients with advanced NSCLC and poor performance status. No significant differences in PFS and OS between patients with or without CTCs at baseline were observed.