MiMedx (MDXG) had the highest return between 2000 and 2008 by a small-cap US stock, returning 4,300%.

ASSET	YEARS	% RETURN
MiMedx (MDXG)	2000-2008	4,300%
Gladstone Capital (GLAD)	2000-2008	2,318.76%
DeFi Technologies (DEFT)	2000-2008	1,780%
Oxley Bridge Acquisition Limited Class A Ordinary Shares (OBA)	2000-2008	1,723.53%
USANA Health Sciences (USNA)	2000-2008	1,309.29%
Nordic American Tankers (NAT)	2000-2008	1,118.23%
Vaalco Energy (EGY)	2000-2008	1,090.41%
EZCORP (EZPW)	2000-2008	1,080.9%
DXP Enterprises (DXPE)	2000-2008	1,013.14%
World Kinect (WKC)	2000-2008	995.16%
National HealthCare (NHC)	2000-2008	947.74%
ATN International (ATNI)	2000-2008	930.57%
Village Super Market (VLGEA)	2000-2008	913.64%
BJs Restaurants (BJRI)	2000-2008	806.98%
Mednax (MD)	2000-2008	805.71%
Healthcare Services (HCSG)	2000-2008	748.85%
Graham (GHM)	2000-2008	745.44%
RPC (RES)	2000-2008	715.6%
Monro Muffler Brake (MNRO)	2000-2008	691.06%
Capitol Federal Financial (CFFN)	2000-2008	684.32%
Sabine Royalty Trust (SBR)	2000-2008	652.72%
Mesabi Trust (MSB)	2000-2008	575.52%
LB Foster (FSTR)	2000-2008	549.98%
Permian Basin Royalty Trust (PBT)	2000-2008	528.12%
Integra LifeSciences (IART)	2000-2008	502.26%

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