Know Labs (KNW) had the highest return between 2006 and 2008 by a small-cap US stock, returning 534,224.4%.

ASSET	YEARS	% RETURN
Know Labs (KNW)	2006-2008	534,224.43%
Gyre Therapeutics (GYRE)	2006-2008	7,448.45%
MiMedx (MDXG)	2006-2008	1,323.03%
OPTIMIZERx (OPRX)	2006-2008	787.14%
Axogen (AXGN)	2006-2008	439.19%
Lineage Cell Therapeutics (LCTX)	2006-2008	433.13%
International Tower Hill Mines (THM)	2006-2008	392.23%
Digital Turbine (APPS)	2006-2008	386.11%
Byrna Technologies (BYRN)	2006-2008	300%
Opko Health (OPK)	2006-2008	295.12%
Universal Insurance (UVE)	2006-2008	276.21%
SIGA Technologies (SIGA)	2006-2008	271.59%
NeoGenomics (NEO)	2006-2008	221.11%
Myriad Genetics (MYGN)	2006-2008	215.67%
EZCORP (EZPW)	2006-2008	199.41%
Artivion (AORT)	2006-2008	185.59%
Compass Minerals International (CMP)	2006-2008	163.41%
Crawford (CRD.B)	2006-2008	158.13%
Sohu (SOHU)	2006-2008	157.28%
Strategic Education (STRA)	2006-2008	135.7%
Diamond Hill Investment (DHIL)	2006-2008	132.81%
SpartanNash (SPTN)	2006-2008	129.03%
Gorman-Rupp (GRC)	2006-2008	128.93%
UFP Technologies (UFPT)	2006-2008	125.11%
Shenandoah Telecommunications (SHEN)	2006-2008	122.24%

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