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AIM: To investigate the differences in clinicopathological features between patients with pancreatic cancer greater or less than 2 cm situated over the pancreatic head and the prognostic factors for survival of patients with pancreatic cancer ＜ 2 cm over the pancreatic head. METHODS: From 1983 to 2006, 159 patients with histologically proven pancreatic adenocarcinoma (PAC) at the pancreatic head undergoing curative resection at the Department of Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan were reviewed, comprising 123 cases of large (L)-PAC (tumor ＞ 2 cm) and 36 cases of small (S)-PAC (tumor ≤ 2 cm). We compared the clinicopathological characteristics and prognosis of L-PAC and S-PAC patients. The clinicopathological characteristics of S-PAC were investigated to clarify the prognosis predictive factors of S-PAC. RESULTS: One hundred and fifty-nine PAC patients, aged 16-93 years (median, 59.0 years) with a tumor at the pancreatic head undergoing intentional curative resection were investigated. The S-PAC and L-PAC patients had similar demographic data, clinical features, and tumor markers (a similar positive rate of carcinoembryonic antigen and carbohydrate antigen 19-9). There were also similar rates of lymph node metastasis, portal vein invasion, stage distribution, tumor differentiation, positive resection margin, surgical morbidity and mortality observed between the two groups. During a follow-up period ranging from 1.0 to 122.7 mo (median, 10.9 mo), S-PAC and L-PAC patients had a similar prognosis after resection (P = 0.4805). Among the S-PAC patients group, patients with higher albumin level (＞ 3.5 g/dL) had more favorable survival than those with lower albumin levels, which was the only favorable predictive prognostic factor. Meanwhile, early-staged (stage Ⅰ, Ⅱ) S-PAC patients tended to have a more favorable outcome than late-stage (stage Ⅲ, Ⅳ) S-PAC patients, but this was not statistically significant. CONCLUSION: S-PAC patients should not be regarded as early PAC. Only higher albumin level (＞ 3.5 g/dL) and early stage disease (stage Ⅰ, Ⅱ) were the favorable prognosis factors for S-PAC patients.