Gd- and Fe-based contrast agents reduce T1 and T2 relaxation times, respectively, are frequently used in MRI, providing improved cancer detection. Recently, contrast agents changing both T1/T2 times, based on core/shell nanoparticles, have been introduced. Although advantages of the T1/T2 agents were shown, MR image contrast of cancerous versus normal adjacent tissue induced by these agents has not yet been analyzed in detail as authors considered changes in cancer MR signal or signal-to-noise ratio after contrast injection rather than changes in signal differences between cancer and normal adjacent tissue. Furthermore, the potential advantages of T1/T2 contrast agents using image manipulation such as subtraction or addition have not been yet discussed in detail. Therefore, we performed theoretical calculations of MR signal in a tumor model using T1-weighted, T2-weighted, and combined images for T1-, T2-, and T1/T2-targeted contrast agents. The results from the tumor model are followed by in vivo experiments using core/shell NaDyF4/NaGdF4 nanoparticles as T1/T2 non-targeted contrast agent in the animal model of triple negative breast cancer. The results show that subtraction of T2-weighted from T1-weighted MR images provides additional increase in the tumor contrast: over two-fold in the tumor model and 12% in the in vivo experiment.