In the treatment of rectal stromal tumors, which account for approximately 5% of gastrointestinal stromal tumors, molecular-targeted neoadjuvant therapy should be considered if the tumor is too large to achieve R0 grade resection or multiple visceral resection is required. Currently, imatinib is generally recommended as the first-line agent for such therapy. Although it has been reported that neoadjuvant therapy in patients experiencing imatinib resistance or intolerable adverse events can be successfully achieved by switching to sunitinib, first-line use of sunitinib for neoadjuvant therapy of gastrointestinal stromal tumors has not previously been reported. In this case report, first-line sunitinib neoadjuvant therapy of two patients who had very large rectal stromal tumors at sites close to the prostate and bladder produced good clinical outcomes.