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Background: Malignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcino-genesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods: By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67,c-Myc and p-JNK. Results: The median immunostaining index of pSmad3C was 79.2％ in low-grade dysplasia,74.9％ in high-grade dysplasia,and 42.0％ in invasive carcinoma ( P < 0.01),whereas that of pSmad3L was 3.4％,4.3％,and 42.4％,respectively ( P < 0.01). There was a negative relationship between the expression of pS-mad3C and c-Myc ( P < 0.001,r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc ( P < 0.001,r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 ( P < 0.01,r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 ( P < 0.01,r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive can-cer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range,0.05–0.93),3.83 (range,0.85–5.96),respectively ( P = 0.02). The median immunostain-ing index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range,0–36.9) and 82.1 (range,46.2–97.1),respectively ( P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7–30.8) and 90.9 (range 52.9–98.5),respectively ( P = 0.02). Conclusions: pSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.