Perspective Therapeutics (CATX) had the highest return between 2000 and 2005 by a small-cap US stock, returning 241,566.7%.

ASSET	YEARS	% RETURN
Perspective Therapeutics (CATX)	2000-2005	241,566.67%
DeFi Technologies (DEFT)	2000-2005	107,600%
Americas Silver (USAS)	2000-2005	5,245.5%
Companhia Siderurgica Nacional ADR (SID)	2000-2005	1,940.78%
BJs Restaurants (BJRI)	2000-2005	1,825.14%
McEwen Mining (MUX)	2000-2005	1,765.12%
Tanzanian Royalty Exploration (TRX)	2000-2005	1,634.29%
USANA Health Sciences (USNA)	2000-2005	1,478.86%
Hovnanian Enterprises (HOV)	2000-2005	1,472.75%
RPC (RES)	2000-2005	1,307.26%
Mednax (MD)	2000-2005	1,165.29%
NAPCO Security Technologies (NSSC)	2000-2005	1,070.27%
Beazer Homes USA (BZH)	2000-2005	1,033.14%
Savara (SVRA)	2000-2005	998.83%
PrimeEnergy (PNRG)	2000-2005	982.11%
World Kinect (WKC)	2000-2005	884.67%
Mesabi Trust (MSB)	2000-2005	878.3%
China Yuchai International (CYD)	2000-2005	877.08%
Tetra Technologies (TTI)	2000-2005	863.85%
Hope Bancorp (HOPE)	2000-2005	752.94%
Consolidated Water (CWCO)	2000-2005	681.52%
Monarch Casino & Resort (MCRI)	2000-2005	669.35%
Flowers Foods (FLO)	2000-2005	620.7%
Nordic American Tankers (NAT)	2000-2005	591.18%
Graham (GHM)	2000-2005	590.43%

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