Extravasation is the situation in which a nuclear medicine injection deposits some fraction of its radioactivity into the soft tissue rather than the bloodstream and may result in a large local radiation dose to tissue. An understanding of localized radiation dose from such unexpected events can be an important aspect of clinical radiation protection. The aim of this study was to estimate and assess absorbed radiation dose to localized soft tissue for hypothetical scenarios of radiopharmaceutical extravasation. Specifically, the goal was to understand whether a radiopharmaceutical extravasation could exceed the US Nuclear Regulatory Commission's medical event reporting limit of 0.5 Sv dose equivalent to tissue or levels at which tissue damage would be anticipated (1.0 Sv dose equivalent). We used the GATE Monte Carlo simulation software to calculate self-dose to spherical volumes containing uniformly distributed amounts of common radiopharmaceutical isotopes. Simulated volumes, radioactivity levels, and effective half-lives represented real-world nuclear medicine procedures. Chosen scenarios consisted of 50 mCi and 100 mCi 177Lu within 20 cm3 and 40 cm3 tissue volumes and a 60 min biological clearance half-time (59.6 min effective half-life), 6 mCi and 12 mCi 99mTc within 1 cm3 and 5 cm3 tissue volumes and a 120 min biological clearance half-time (90 min effective half-life), and 3 mCi and 6 mCi 18F within 1 cm3 and 5 cm3 tissue volumes with a 30 min biological clearance half-time (23.6 min effective half-life). We calculated absorbed doses to be between 5.5 Gy and 23.5 Gy for 177Lu, between 0.9 Gy and 12.4 Gy for 99mTc, and between 1.5 Gy and 16.2 Gy for 18F. Radiopharmaceutical extravasations can result in tissue doses that surpass both medical event reporting limits and levels at which deterministic effects are expected. Radiation safety programs should include identification, mitigation, dosimetry, and documentation of significant extravasation events.