Minimally invasive systems and methods for navigation-assisted surgery are described. The system comprises a patient reference device and a transmitter. The patient reference device comprises a microsensor disposed at a distal end. The distal end is configured to pierce a patient's skin and to be anchored in a patient's anatomy. The microsensor is at least partially embedded in the patient's anatomy and is anchored proximate to a surgical field of interest. The transmitter is configured to be detachably attached to the patient's skin proximate to the surgical field of interest. The system establishes a global navigation reference frame by transmitting signals from the transmitter and receiving the signals with the microsensor to establish a position and an orientation of the microsensor to register a position and an orientation of the patient's anatomy within the global navigation reference frame. Other embodiments are described.