Background and Objective In an attempt to develop a new therapeutic approach for highly localized thermal destruction of tissue targets that lack natural pigmentation, the potential of in-vivo dye-enhanced photothermal therapy (PTT) was investigated. PTT involves the application of an exogenous absorber, which accumulates in metabolically active tissues, followed by non-invasive light irradiation, using appropriate wavelengths, exposure durations, and irradiances. The chromophore used, palladium(II) octabutoxynaphthalocyanine (PdNc(OBu)8), strongly absorbs in the near infrared wavelength range which thus permits good penetration depth of the exciting light. The predominant de-excitation routes of the chromophore are radiationless thermal processes. Materials and Methods Using a BALB/c mouse model with a subcutaneously implanted syngeneic EMT6 adenocarcinoma, 96-100 hours after intraperitoneal application of PdNc(OBu)8, tumor, and surrounding tissue were irradiated with a 830 nm continuous wave diode laser applying 30 Wcm-2 for 10-20 seconds. Treatment parameters were based on theoretical calculations. Results Histological evaluation of thermal effects on tumor and normal tissue showed that after PdNc(OBu)8-enhanced photothermal treatment, highly localized and selective thermal damage of the tumors was achieved. The necrotic tumor area was invaded by inflammatory cells, including neutrophils, macrophages, mast cells, and lymphocytes, thus reflecting a prominent host immune response. In tumors treated with PTT for 15 or 20 seconds, respectively, only few surviving tumor cells were detected underneath the epidermis. Adjacent peripheral normal tissue including skin and muscle remained completely unaffected. Conclusion This study highlights the potential of achieving irreversible thermal tissue damage closely localized to the target tissue when PdNc(OBu)8 is used in combination with continuous-wave light.