Background: Transcutaneous bilirubinometry is an effective screening method for neonatal hyperbilirubinemia. Current transcutaneous bilirubin (TcB) meters are designed for the “standard” situation of TcB determinations on the forehead or sternum of term newborns. We hypothesize that skin anatomy can considerably influence TcB determinations in non-standard situations—e.g., on preterm newborns or alternative body locations. Methods: A commercially available TcB meter (JM-105) was evaluated in vitro on phantoms that accurately mimic neonatal skin. We varied the mimicked cutaneous hemoglobin content (0–2.5 g/L), bone depth (0.26–5.26 mm), and skin maturity-related light scattering (1.36–2.27 mm−1) within the clinical range and investigated their influence on the TcB determination. To obtain a reference frame for bone depth at the forehead, magnetic resonance head scans of 46 newborns were evaluated. Results: The TcB meter adequately corrected for mimicked hemoglobin content. However, TcB determinations were influenced considerably by clinically realistic variations in mimicked bone depth and light scattering (deviations up to 72 µmol/L). This greatly exceeds the specified accuracy of the device (±25.5 µmol/L). Conclusion: As bone depth and light scattering vary with gestational maturity and body location, caretakers should be cautious when interpreting TcB measurements on premature newborns and non-standard body locations.