<b><i>Introduction:</i></b> Oncological second opinions are becoming increasingly important in the era of complex treatments and established certified cancer centers. Oncological guidelines with the highest levels of evidence are available, but these can only be effective to the extent that they are implemented. Therefore, we analyzed the effects of second opinions with regard to their agreement with first opinions and conformity with guidelines. <b><i>Methods:</i></b> In 164 patients with a diagnosis of breast cancer or gynecological malignancy who requested a second opinion, the first and second opinions, established at the interdisciplinary tumor conference, and conformity with the guidelines were evaluated. <b><i>Results:</i></b> The first opinion was not in agreement with the guidelines in 34.8% (15.2% diagnosis, 12.8% surgical therapy, 13.4% systemic therapy, and 5.5% radiotherapy), and the recommendations were optimized in the second opinion in 56.7% (28.7% diagnosis, 15.9% surgical therapy, 30.5% systemic therapy, and 8.5% radiotherapy). <b><i>Conclusions:</i></b> Oncological second opinions showed significant effects and one-third of first opinions were not in conformity with the guidelines. In a significant proportion of cases, the existing treatment plan was changed or supplemented to allow modern and individualized treatment approaches.