Background: Signet-ring cell carcinoma of the stomach (SRCC) is significantly associated with poor prognosis and low treatment effectiveness, compared to adenocarcinoma of the stomach (AC). One of the causes of SRCC aggressive course can be its diffuse invasive growth pattern. The ability of tumor cells to synthesize and/or capture growth factors ensures the independent tumor development. VEGF, EGF, IGFI and EGFII facilitate neoangiogenesis and regulation of malignant processes in paracrine/autocrine mechanisms. The purpose of the study was to find the difference between local levels of VEGF, EGF, IGFI and IGFII in tumor and intact tissues in AC and SRCC. Methods: Levels of VEGF, EGF, EGFR, IGF-I and IGFII were determined by ELISA in tumor and intact gastric tissues of 15 AC patients and 10 SRCC patients (T_2-3N_0-2M₀, G_2-3), mean age 62.8±2.38 years. Results: Levels of IGF-I, IGF-II and VEGF in intact gastric tissues were similar in AC and SRCC. EGF and EGFR levels in AC were 2.9 and 1.5 higher than in SRCC. Levels of VEGF in AC tumor tissues, compared to intact gastric tissues, increased by 2.3 times, EGF and EGFR did not change, and IGFI and IGFII decreased by 2.1 and 1.8 times, respectively. Tumor tissues of SRCC patients showed the increased levels of EGF (by 2.9 times) and EGFR (by 1.8 times); VEGF and IGF were similar to the levels in intact tissues. SRCC was characterized by the activation of systems of EGF and IGF, but not VEGF. AC demonstrated the stimulation of VEGFA neoangiogenesis. Conclusions: The activation of systems of EGF and IGF in SRCC could be associated with some characteristics of the diffuse growth pattern and the tumor origin from neuroendocrine cells which facilitates the autocrine/paracrine regulation of the invasive growth. AC requires neoangiogenesis which is realized primarily by the VEGF system.