Kevin Conroy, vice president and general counsel, will replace Puisis. Conroy will also join Third Wave's board.
In a statement, Puisis said he came to Third Wave "and stayed for a specific purpose. With a new business model and ... management team in place, that purpose has been completed.
"Given that we fundamentally have a new company, I believe this is an excellent time to make the switch," Puisis added.
Puisis is credited with helping to engineer Third Wave's evolution from a tool vendor into a molecular diagnostics player.
Conroy, 40 years old, came to Third Wave from GE Healthcare, where he helped integrate the firm's acquisition of Instrumentarium Corp. A former lawyer, he also helped develop, manage, and grow the intellectual property portfolio of GE's its $1.3-billion patient-monitoring, medical imaging, and health care software business.