Gastrointestinal pythiosis is a severe, progressive and often a fatal disease, which is caused by the aquatic pathogen Pythium insidiosum. Treatment is challenging due to the disease's resistance to antifungal drugs. Surgical resection is frequently attempted in cases of pythiosis; however, it can be technically challenging. This report presents two dogs with decreased appetite, abdominal pain, progressive haematochezia, tenesmus and significant weight loss. With the medical histories of both being young canines, living in areas with access to natural water resources and with the main chronic gastrointestinal symptoms having not responded to symptomatic treatment, pythiosis was taken into consideration. Abdominal ultrasound revealed severe, diffuse thickening and loss of normal layering of the colonic wall. These findings led to a differential diagnosis between intestinal neoplasia and fungal disease. Full‐thickness biopsies were later performed, and immunohistochemistry staining was suggested for colonic pythiosis. Medical treatment for pythiosis was successful with a combination of oral terbinafine and prednisolone. However, therapy with itraconazole in case 1 did not improve the clinical signs, and in case 2, itraconazole was used after all clinical signs have improved for clinical control. Since then, there has been no recurrence of clinical signs until the time of preparing this report (19 months for case 1, 11 months for case 2 since the cessation of treatment). The treatment was successful based on clinical signs and ultrasonographic data, and the disease remission was not confirmed by advance imaging, monitoring of pythiosis enzyme‐linked immunosorbent essay concentration or repeat sampling.