Know Labs (KNW) had the highest return between 2000 and 2007 by a small-cap US stock, returning 763,220.6%.

ASSET	YEARS	% RETURN
Know Labs (KNW)	2000-2007	763,220.61%
Perspective Therapeutics (CATX)	2000-2007	669,900%
OPTIMIZERx (OPRX)	2000-2007	149,900%
Gyre Therapeutics (GYRE)	2000-2007	17,414.09%
Cryoport (CYRX)	2000-2007	15,727.03%
Mednax (MD)	2000-2007	1,847.14%
Lsb Industries (LXU)	2000-2007	1,821.38%
DXP Enterprises (DXPE)	2000-2007	1,678.29%
SunOpta (STKL)	2000-2007	1,543.08%
Graham (GHM)	2000-2007	1,530.89%
McEwen Mining (MUX)	2000-2007	1,500.23%
USANA Health Sciences (USNA)	2000-2007	1,426.18%
Flotek Industries (FTK)	2000-2007	1,401.67%
Byrna Technologies (BYRN)	2000-2007	1,300%
Mesabi Trust (MSB)	2000-2007	1,269.9%
BJs Restaurants (BJRI)	2000-2007	1,269.33%
Helios Technologies (HLIO)	2000-2007	1,242.67%
Andersons (ANDE)	2000-2007	1,183.8%
China Yuchai International (CYD)	2000-2007	1,152.51%
Digital Turbine (APPS)	2000-2007	1,150%
Astronics (ATRO)	2000-2007	1,017.88%
Healthcare Services (HCSG)	2000-2007	989.87%
NAPCO Security Technologies (NSSC)	2000-2007	958.8%
National HealthCare (NHC)	2000-2007	949.38%
Nordic American Tankers (NAT)	2000-2007	933.86%

Small-cap stocks are treated as having a market cap between $300M and $2B.