Background Many studies have shown that cancer cell differentiation and microvascular invasion play a principle role in cancer progression and metastasis, and non-invasive imaging techniques such as CT, MRI and US assessing the differentiation and the surgical resectibility and the prognosis of cancers are now of great importance. This study aimed to explore the correlation of triple-phase multi-slice CT scan with the histological differentiation and intratumor microvascular/lymphatic invasion of progressive gastric cancer.Methods The present study included 64 patients with gastric cancer, all of whom underwent routinal and dual-phase contrast enhancement multi-slice CT examinations of the upper abdomen before surgery. The post-operative specimens were used for determination of histological differentiation, cancer cell invasion of intratumoral microvascular/lphatic vessel identified by CD34 and D2-40 expression. Correlations between contrast enhancement ratio (CER) of triple-phase multi-slice CT scan in gastric cancer and histological differentiation as well as intratoral microvascular/lymphatic invasion were compared and analyzed.Results There was a significant correlation between CER of triple-phase CT scan in gastric cancer and tumor histological differentiation (P＜0.05). CER of the arterial phase in gastric cancer with intratumoral microvascular invasion was significantly higher than that without invasion (0.61±0.28 vs. 0.46±0.14, P ＜0.05); CER of the arterial-parenchymal phase was significantly lower in gastric cancer with intratumoral microvascular invasion than that without invasion (1.81±0.39 vs. 2.28±0.80, P＜0.05). However, CER of the parenchymal phase in gastric cancer with intratumoral lymphatic invasion was significantly higher than that without invasion (1.25±0.57 vs. 1.00±0.35, P＜0.05).Conclusions CER of triple-phase multi-slice CT scan in gastric cancer is closely correlated with intratumoral microvascular and lymphatic invasion, and also could be used as a marker for histological differentiation.