MS-DOS paint program in 16 bytes found at http://www.sizecoding.org/wiki/Paint16b

paint16b.asm

org 100h        ; code starts at 0x100
mov al,0x12     ; assume ah = 0 ; set graphics mode to 640*480
inc bx          ; assume bx = 0 ; set to 1 (show cursor)
mloop:	
int 0x10        ; first loop, switch to graphic mode
                ; further loops, set pixel		
xchg bx,ax      ; first loop, set AX to 1 (show cursor)
                ; further loops, restore old calling mode		
xor al,0x02     ; switch modes : show cursor <-> get mouse state
                ; updating XY every second loop plus drawing
                ; one pixel left results in thicker lines		
int 0x33        ; call the mouse interrupt
xchg bx,ax      ; store the button state in AL for drawing
                ; remember the current calling mode
                ; for switching it later (in BX)			
mov ah,0x0C     ; set mode to "set pixel"
loop mloop      ; dec CX -> draw one pixel left from cursor
                ; basically enables drawing pixels
                ; while the cursor is active
                ; allows exit if the mouse is leftmost
ret             ; assume [[FFEE]] = [0] = CD20 = int 20

Requirements

NASM - The Netwide Assembler and DOSBox, an x86 emulator with DOS

If you are using macOS and have Homebrew installed then you can install them like this:

brew install nasm dosbox

Assembling the binary

nasm paint16b.asm -f bin -o paint16b.com

Running the program in dosbox

dosbox -c "MOUNT C `pwd`" -c "C:" -c "paint16b.com"

How it looks