Neuropathic cancer pain represents a major challenge. Treatment often requires adjuvant analgesics, including gabapentin, to complement the effects of opioids. This study aimed to compare the effectiveness and safety of gabapentin combined with an opioid versus opioid monotherapy for the management of neuropathic cancer pain. Seventy-five cancer patients who were receiving opioid therapy and reported sufficient pain relief of nociceptive, but not neuropathic, pain were enrolled. Sixty-three patients completed the study. Patients were randomized to one of the following treatment protocols: 1) gabapentin adjuvant to ongoing opioid treatment titrated according to pain response while opioid dose was kept constant (group GO), and 2) continuation of opioid monotherapy according to the World Health Organization treatment ladder approach (group OO). Changes in pain intensity, allodynia, and analgesic drug consumption were evaluated at Day 4 and Day 13. Side effects were also recorded. Both treatments resulted in a significant reduction of pain intentsity at Day 4 and Day 13 compared to baseline. However, mean pain intensity for burning and shooting pain was significantly higher in the OO group compared to the GO group at both the fourth (P = 0.0001) and 13th (P = 0.0001) days of the study. An earlier significant decrease (at Day 4, P = 0.002) was observed for allodynia in the GO group compared to the OO group. The rate of side effects in the GO group was significantly lower than that in the OO group (P = 0.015). These data suggest that gabapentin added to an opioid provides better relief of neuropathic pain in cancer patients than opioid monotherapy; this combination of gabapentin and an opioid may represent a potential first-line regimen for the management of pain in these patients.