Previously we investigated the anticancer activity of bacteriophage preparations in various murine tumor models. We demonstrated the antimetastatic activity of purified and nonpurified bacteriophage preparations injected intraperitoneally (IP). However, in solid tumors we observed antitumor activity of purified bacteriophages, but the lysates (raw preparations obtained by culturing phages with bacteria) stimulated tumor growth. In this article we present a comparison of the antitumor activity of bacteriophages after oral (per os, PO) and IP administration of lysates and purified preparations. Our observations indicate that PO application of a bacteriophage preparation is safer and at least as effective as IP. Stimulation of solid tumors by lysates administered orally was not observed, and bacteriophages applied PO were more effective in inhibiting metastases formation. These observations are of great importance in any consideration of possible therapeutic applications of bacteriophages. The role of the route of bacteriophage administration should be considered in the context of the effectiveness and safety of such therapies.